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Topical Nutlin-3 Potentiates the UVB-induced p53 Response and Reduces DNA Photodamage and Apoptosis in Mouse Epidermal Keratinocytes in Vivo

Author(s): Catharina M. Lerche

Journal: Journal of Clinical & Experimental Dermatology Research
ISSN 2155-9554

Volume: 1;
Issue: 2;
Date: 2010;
Original page

Keywords: Nutlin-3 | p53 | Apoptosis | Thymine dimer | Hairless mice

Background/Aims: (-)-Nutlin-3 (nutlin) is a cis-imidazoline analog, which activates p53 by antagonizing murine double minute (Mdm2) protein. To our knowledge, no studies have assessed the effect of topical nutlin on cyclobutane pyrimidine dimers (CPD) repair and apoptosis. We therefore conducted a study in hairless mice to investigate the effect of topical nutlin on murine epidermis after UVB-radiation. Methods: Female C3.Cg/TifBomTac immunocompetent mice were treated with 100 µl 43 mM nutlin 30 min before and after irradiation with 3 SED (100 mJ/cm2) UVB. Animals were euthanized 24 hours after irradiation, the dorsal, treated skin was biopsied and fixed in 4% formalin. Sections were incubated with the antibodies against p53, thymine dimers and terminal deoxynucleotidyl transferase-mediated dUTP nick and labelling (TUNEL). Results: We showed here that nutlin was active after topical application in hairless mice and potentiated the p53 nuclear translocation in epidermal keratinocytes after ultraviolet B irradiation. Moreover, topical treatment with nutlin resulted in a decrease in the number of keratinocytes exhibiting positive nuclear staining for thymine dimers (P

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